Minocycline

Summary
Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing-remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study.Mult Scler. 2009 Sep 23 epub ahead of print

Details
Canadian researchers, lead by Dr. Luanne Metz of Calgary,aimed to investigate the efficacy of combined glatiramer acetate(GA) plus minocycline treatment in people with relapsing-remitting MS, by comparing a group receiving GA plus minocycline with another receiving GA plus placebo. Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study.

Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63%, the total number of new and enlarging T2 lesions by 65%, and the total T2 disease burden.  A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging. The risk of relapse tended to be lower in the combination group.

Treatment was safe and well tolerated. The authors conclude that results showed a consistent trend favouring combination treatment.

As minocycline is a relatively safe oral therapy, The authors conclude that further study of this combination is warranted in relapsing-remitting multiple sclerosis.

Source: Multiple Sclerosis Society of Canada (14/10/09)

The scientists reported that in a clinical trial of patients with amyotrophic lateral sclerosis or Lou Gehrig's disease, those who received the drug minocycline declined more rapidly than those who received a placebo.

Their report, published Thursday in the journal Lancet Neurology, comes just a week after the Multiple Sclerosis Society of Canada announced it was funding a multi-centre Phase 3 trial to look at whether the inexpensive and off-patent minocycline can slow the progression of MS when treatment is commenced in the earliest stages of the disease.

One of the lead researchers in the MS study, Dr. Wee Yong of the University of Calgary, admitted the U.S. findings gave him pause when he heard them presented in April at a meeting of the American Academy of Neurology.

But Yong said he thinks the trial should proceed.

"We will of course be cautious," Yong said in an interview.

"We are always cautious in a clinical trial. But we don't really want to kill anything too early because of what is observed in another context which may not have any bearing to the current condition that we're trying to treat."

"I should point out that we are dealing with different diseases altogether. The pathology or the reason for ALS is very much different from the pathophysiology of MS."

The U.S. researchers were studying minocycline as a possible therapy for ALS, a progressive and eventually fatal degeneration of motor neurons which destroys the brain's ability to instruct the body to move.

The study was led out of Columbia University Medical Center in New York, but involved investigators from medical institutions across the United States.

Testing in mice genetically engineered to suffer from ALS showed the drug was beneficial. Likewise early testing in humans - the small Phase 1 and 2 trials designed to establish safety and look for early signs of efficacy - were sufficiently positive to allow the researchers to proceed to a larger and more expensive Phase 3 trial.

But there, to their surprise, they discovered that people taking the drug declined and died more rapidly than people who received a placebo.

"We were shocked. We were just absolutely stunned when we saw these results," one of the lead investigators, Dr. Robert Miller, said from San Francisco, where he is director of the Forbes Norris ALS Research Center at California Pacific Medical Center Research Institute.

"That was our first thought. But our second thought was that we need to get these results out because we need to avoid this happening to other people with other diseases. And we were just very worried that people ... if they didn't know about our experience that they would just move helter-skelter into testing this in other people and maybe cause more harm than good."

Miller and his co-authors admitted in the article that their animal model may have been faulty, or they may have been using too high a dose of the drug.

But they also cautioned researchers who are studying minocycline as a potential therapy for conditions such as Parkinson's and Huntington's diseases, stroke and MS to take note of their results.

"The justification for these trials should be reassessed in light of our findings: minocycline might have a detrimental effect on patients with neurological diseases other than ALS," they wrote.

Yong and his colleagues have also conducted animal studies and Phase 1 and 2 clinical trials in humans and have seen nothing that suggests minocycline would be harmful in MS patients.

Their decision to push on with their work was supported by Dr. Fred Lublin, director of the MS Center at Mount Sinai School of Medicine in New York.

"ALS and MS are very different diseases," Lublin said. "Different mechanisms, different types of degeneration."

"It raises a flag of caution but it doesn't necessarily change what they ought to be doing, based on their Phase 2 data."

He suggested, however, that the Canadian investigators will need to keep a very close eye on the safety data generated in the trial.

Source: The Canadian Press Copyright © 2007 The Canadian Press. All rights reserved. (01/11/07)

A common acne medication that has been available for over 30 years has the potential to delay the progress of multiple sclerosis and if proven effective, will offer an inexpensive option for the treatment of early MS, says the MS Society of Canada.

Clinical researchers in Calgary and 13 other Canadian centres will be taking an in-depth look at an oral therapy known as minocycline after initial studies have shown promising results. A new $4 million multi-centre clinical trial involving 200 participants from across Canada is being funded through the MS Society's related MS Scientific Research Foundation.

"The benefits of minocycline are straight forward: it's relatively cheap, has few side effects and can be taken in pill format, " says Dr. Luanne Metz, principal investigator for the study and a professor of clinical neurosciences at the University of Calgary Faculty of Medicine. "The aim of our research is to see if this common drug can reduce the occurrence of further disease activity in people who have experienced an initial attack of MS symptoms and who are at high risk of progressing to definite MS. Without treatment, two thirds of people facing this circumstance are expected to be diagnosed with MS within 6 months. We believe minocycline can reduce this number."

In MS, myelin, which is the protective coating of the nerve fibres of the brain and spinal cord, becomes inflamed. This inflammation can be seen as characteristic lesions by magnetic resonance imaging (MRI). Previous clinical tests of minocycline have shown an 84 per cent reduction of MS lesion activity on MRI.

"There is obvious benefit in delaying the rate of disease progression in MS, from improved quality of life to reduced healthcare expenses," says Dr. William McIlroy, national medical advisor for the MS Society of Canada. "The breadth of the study, the reputation of the researchers involved and the early clinical data supports the view that there is considerable promise for minocycline. We would not be involved if this were not the case."

Minocycline works by inhibiting the activities of an enzyme and immune cells that are keys to initiating MS attacks. It has been used in acne treatment for its anti-bacterial effects but studies have shown its anti-inflammatory properties could be important factors in slowing down MS. These insights were discovered through pioneering research funded by the MS Society of Canada and led by Dr. V. Wee Yong at the University of Calgary (U of C). Drs. Metz and Yong lead the MS program at the Hotchkiss Brain Institute at U of C where many of the early studies on minocycline took place.

In comparing minocycline to current therapies, the cost savings would be substantial. In generic form, minocycline is available for as low as $800 per year. Current MS therapies can cost between $18,000 and $40,000 per year. Researchers note that minocycline would not necessarily replace current therapies, but might delay the timeframe in which they would be required.

The study will be randomized and double-blind by design. Investigators will compare 100 mg of oral minocycline twice daily to placebo over a period of two years.

Enrolment will begin in early 2008 and 14 MS clinics are involved including institutions in Calgary, Vancouver, Burnaby, Edmonton, Red Deer, Saskatoon, London, Toronto, Kingston, Ottawa, Montreal, Quebec City, Sherbrooke and Halifax.

Source: MS Society of Canada © 2007 Marketwire, Incorporated (26/10/07)

Researchers at the University of Wisconsin and the Max-Planck Institute in Germany reported they have successfully treated rats with the animal model for multiple sclerosis with the antibiotic drug Minocycline. When the animals were treated before the disease began, the treatment reduced disease activity. When they were treated after symptoms had developed, disease severity was reduced and progression stopped.

A pilot study of Minocycline as a treatment for MS is already underway at the University of Calgary. It involves 12 people with MS, and is part of a larger study to determine the role that substances called matrix metalloproteinases (MMPs) play in both the attack on myelin and in myelin maintenance and repair. The MMP study is headed by Dr. Voon Wee Yong. Dr. Luanne Metz heads the clinical portion of the project. Results from the pilot study of minocycline should be available later this year.

Researchers believe this antibiotic could be used in early multiple sclerosis or prior to relapses of the disease. Minocycline is already used in another autoimmune disorder, rheumatoid arthritis.

For further information, refer to the BBC article.

Source: BBC News (09/01/06)

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